Study of the immunopathogenesis of X-linked lymphoproliferative syndrome (XLP) and phenotypes of aplastic anemia, agammaglobulinemia, fatal or chronic infectious mononucleosis (IM) and malignant lymphoma (ML) and related immunodeficiency/lymphoproliferative disorders is done by developing individual XLP, fatal infectious mononucleosis and EBV infections, familial lymphoproliferative malignancy syndrome-registries to test hypotheses that specific immunodeficiency/lymphoproliferative disorders can arise owing to inherited or acquired immune deficiency to Epstein-Barr virus (EBV), chromosomal breakage or immunoregulatory T-cell defects. Comprehensive studies include: (1)\virological testing with Monospot, heterophile, EB-specific markers, (anti-early antigen, -viral capsid antigen), and -EB nuclear-associated antigen (EBNA) antibodies, EB genome detection by filter cRNA/DNA and vDNA/DNA renaturation kinetic and in situ hybridization studies, spontaneous cell line establishment, and transformation of cord cells with throat washings; (2)\genetic studies such as pedigree analysis, screening for XLP (challenging males at risk with OX 174), doing EBV-specific serology, measuring spontaneous and induced chromosomal breakage of leukocytes by sister chromatid exchange and karyotyping, performing linkage studies for Xga blood group, G-6PD, and HLA-DR; and (3)\immunopathological studies including blood count and morphology, immunoglobulin quantitation, T-\and B-cell subpopulation enumeration in an activated-cell sorter, in vitro evaluation for lytic/suppressor and memory cell activity by testing leukocyte migration inhibition to EBV antigens, T-cell inhibition of EBV-infected cell outgrowth and reverse hemolytic plaque formation, comparing responses to EBV and pokeweed mitogen, assaying interferon and thymosin, and studying all organs to identify the cells producing lesions. Clonality of ML is determined by using simultaneous cell surface marking, karyotyping and EBNA staining of lymphoid cells to test the hypothesis that polyclonal IM can convert to monoclonal ML via a specific cytogenetic error. The registries provide an opportunity for consultation, diagnosis, counseling and therapy and are a repository for biological specimens for prospective studies.